ArticlesRandomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease
Introduction
Despite advances in the treatment of congestive heart failure, the outlook for many patients with this disorder remains poor. In patients with mild or moderate symptoms who receive standard treatment including an inhibitor of angiotensin-converting enzyme (ACE), the annual rate of hospital admission is about 15–20% and the mortality rate about 10%.1 Treatment with β-blockers may have the potential to reduce morbidity and mortality in heart failure, but there is no unequivocal evidence as yet.2 However, 3–6 months of treatment with a β-blocker has been clearly shown to increase left-ventricular ejection fraction by about 5% (absolute units) in patients with heart failure of idiopathic2 or ischaemic3 aetiology. Such therapy has not produced any consistent effects on symptoms or exercise performance,2, 3 and whether longer-term treatment will produce clearer benefits for these outcomes or for serious morbidity and mortality remains unclear.
We report here the final results from the Australia/New Zealand Heart Failure Research Collaborative Group trial of carvedilol in 415 patients with heart failure due to ischaemic heart disease. Carvedilol is a β-blocker with β1-blocking vasodilator properties and with several other potentially advantageous effects, including antioxidant and anti-ischaemic properties.4 A planned interim analysis from this study after 6 months of follow-up showed an absolute increase of 5·2% in left-ventricular ejection fraction, a reduction in left-ventricular dimensions, no change in exercise performance, and a trend to worsening of symptoms of heart failure among patients assigned carvedilol.3 We now provide data on the same outcomes after 12 months of follow-up, as well as the risks of death, hospital admission, or worsening heart failure during an average of 19 months of follow-up.
Section snippets
Patients
Participants were recruited to the trial from 20 hospitals in Australia and New Zealand. Potentially eligible patients had chronic stable heart failure due to ischaemic heart disease (defined as a documented history of myocardial infarction, typical angina, an exercise electrocardiogram positive for ischaemia, or angiographic evidence of coronary disease) and a left-ventricular ejection fraction by radionuclide ventriculography of less than 45%, and were of current New York Heart Association
Results
The mean age of the participants at entry to the study was 67 years, and 80% were men. 70% were classified as being NYHA functional class II or III at the time of randomisation, and 43% had previously been class IV (table 1). Almost 90% had a history of myocardial infarction, and 42% had had a previous hospital admission for heart failure. 95% were currently receiving drug treatment for the management of heart failure, and 85% were receiving ACE-inhibitor therapy. The average leftventricular
Discussion
We have found that in patients with chronic stable heart failure due to ischaemic heart disease, the effects of carvedilol on left-ventricular function were maintained for at least a year from the start of treatment, with no apparent loss of the initial short-term improvement. These effects were achieved against a background of standard drug therapy for heart failure, including ACE inhibitors for more than 80% of patients. The increase in left-ventricular ejection fraction and the decrease in
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